Genetic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health & Human Services, Bethesda, MD 20892-7236, USA.
Previous small studies have reported familial clustering of myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). We identified 6217 PV, 2838 ET, 1172 MF, and 812 MPN unclassifiable (NOS) patients diagnosed in Sweden, 43 550 controls, and first-degree relatives of cases (n = 24 577) and controls (n = 99 542). Using a marginal survival model, we calculated relative risks (RRs) and 95% confidence intervals as measures of familial aggregation. Relatives of MPN patients had significantly increased risks of PV (RR = 5.7; 3.5-9.1), ET (RR = 7.4; 3.7-14.8), and MPN NOS (RR = 7.5; 2.7-20.8). Analyses stratified by type of first-degree relative revealed consistently higher risks for siblings, compatible with a model of recessive genetic inheritance, which can be confirmed only by identifying the susceptibility gene(s). Mean age at MPN diagnosis was not different (P = .20) for affected relatives of cases (57.5 years) versus controls (60.6 years), and risk of MPN by age was not different for parents versus offspring of MPN cases (P = .10), providing no support for anticipation. Relatives of MPN patients had a borderline increased risk of chronic myeloid leukemia (CML; RR = 1.9; 0.9-3.8; P = .09). Our findings of 5- to 7-fold elevated risk of MPNs among first-degree relatives of MPN patients support the hypothesis that common, strong, shared susceptibility genes predispose to PV, ET, MF, and possibly CML.
"Even before identifying a common mutation associated with the development of cMPN, family clusters of patients sharing various types of these disorders had already been identified (8). Landgren et al. (9) studied the risk of PV, ET and MF development among the first-degree relatives of patients who had been previously diagnosed with cMPN. First-degree relatives were observed to have a five to seven times greater risk of developing cMPN, particularly in certain probands, suggesting that family members may share some of the oncogenes involved in myeloproliferative disorders. "
[Show abstract][Hide abstract] ABSTRACT: The JAK2 46/1 haplotype has recently been described as a major contributing factor to the development of myeloproliferative neoplasm, whether positive or negative forthe JAK2 V617F mutation. The G allele, identified by a single-nucleotide polymorphism known as JAK2 rs10974944, is part of the JAK2 46/1 haplotype. The aim of this study was to verify the association between the presence of the G allele and the development of BCR-ABL-negative chronic myeloproliferative neoplasms in our population.
Blood and oral mucosa swab samples were obtained from 56 patients of two local Brazilian hospitals who had previously been diagnosed with BCR-ABL-negative chronic myeloproliferative neoplasms. Blood samples from 90 local blood donors were used as controls. The presence of the G allele was assessed using a PCR-RFLP assay after extracting DNA from the samples.
The presence of the G allele was strongly associated with the presence of BCR-ABL-negative chronic myeloproliferative neoplasms (p = 0.0001; OR = 2.674; 95% CI = 1.630-4.385) in the studied population.
In agreement with previous reports, the JAK2 46/1 haplotype, represented in this study by the presence of the G allele, is an important predisposing factor in the oncogenetic development of these neoplasms in our population.
"The higher risk of kidney cancer in PV patients and the higher risk of PV in patients with adrenal tumours raise the suspicion that some patients with secondary erythrocytosis may be erroneously diagnosed with PV. No data was available to provide molecular basis for the confirmation of diagnosis of PV cases, although accuracy of diagnostic accuracy of haematological disorders in Sweden is over 90–95% (Landgren et al, 2008). "
"The resultant JAK2 V617F mutation in the bone marrow stem cell confers a loss of auto-inhibitory control and an overproduction of the various cell-types. Although PV is not considered a hereditary disease, familial clustering of cases has been reported [5,6]. In addition, three recent studies [7–9] all demonstrated that the malignant clone containing the JAK2 mutation is strongly associated with a particular germ line haplotype encompassing the JAK2 gene. "
[Show abstract][Hide abstract] ABSTRACT: Cancer cluster investigations rarely receive significant public health resource allocations due to numerous inherent challenges and the limited success of past efforts. In 2008, a cluster of polycythemia vera, a rare blood cancer with unknown etiology, was identified in northeast Pennsylvania. A multidisciplinary group of federal and state agencies, academic institutions, and local healthcare providers subsequently developed a multifaceted research portfolio designed to better understand the cause of the cluster. This research agenda represents a unique and important opportunity to demonstrate that cancer cluster investigations can produce desirable public health and scientific outcomes when necessary resources are available.
International Journal of Environmental Research and Public Health 03/2010; 7(3):1139-52. DOI:10.3390/ijerph7031139 · 2.06 Impact Factor
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